CORE B: CLINICAL - ABSTRACT The Clinical Core clinically and neuropsychologically characterizes, and longitudinally follows, a cohort of cognitively-normal elderly control (NC) subjects and patients with Alzheimer's disease (AD), Mild Cognitive Impairment (MCI), Dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Frontotemporal dementia (FTD) or other dementing disorders. It also banks biological specimens (e.g., plasma, DNA, fibroblasts, CSF) from these subjects and facilitates autopsy. Over the past 30 years, the Core has provided well-characterized subjects, clinical and cognitive data, and biological specimens to local, national and international research that has contributed to great progress in the areas of detection of AD in its earliest (even pre-clinical) stages, differential diagnosis of AD from other dementias, tracking the course of AD over time, and testing new treatment approaches for AD. The Specific Aims of the Clinical Core are to: (1) Maintain and follow a panel of about 500 well characterized English- or Spanish-speaking subjects with AD, MCI, DLB/PDD, or FTD, and age- and education-matched NC subjects. (2) Maintain a high autopsy rate (i.e., greater than 75%). (3) Perform annual detailed and standardized nursing, neurological, and neuropsychological evaluations of all subjects using Uniform Data Set (UDS) and supplemental procedures. (4) Maintain and augment banks of plasma, DNA, and CSF from subjects with AD, MCI, DLB/PDD and healthy controls. (6) Share clinical data with the NACC UDS and with investigators performing other multi-center analyses of clinical data. (7) Participate in projects with other ADCs, in ADNI, and in multi-center therapeutic drug trials for AD. (8) Refine and evaluate clinical and neuropsychological assessment procedures for accurate identification of the transition from normal cognition and pre-clinical AD to MCI to very mild AD dementia. (9) Refine and evaluate clinical, neuropsychological, and laboratory assessment procedures to differentiate AD from DLB/PDD, FTD, and other dementing disorders. The Core will also engage in innovative developmental research that will examine novel neuropsychological approaches to early detection of AD, assess subjective memory and other cognitive complaints, and assess attitudes and potential barriers to participation in primary prevention clinical trials. This will be enhanced by new recruitment of cognitively normal elderly with increased risk of AD (due to age and APOE genotype) and willingness to undergo typical AD trial procedures (including neuroimaging and plasma and CSF biomarkers). This cohort will provide important ecological validity in relation to enrollment for future primary prevention clinical trials.